Certain embodiments of the invention provide a method of detecting the presence of a biomarker associated with resistance to an mTOR kinase inhibitor in a subject, comprising determining the presence of the biomarker in a physiological sample from the subject, wherein the sample comprises a nucleic acid.

Provided herein are methods, compounds, and compositions for reducing expression of a nrRNA in an animal. Also provided herein are methods, compounds, and compositions for treating, ameliorating, delaying or reducing a symptom of a disease or disorder associated with a nuclear-retained RNA in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a disease or condition associated with a nuclear-retained RNA, or a symptom thereof.

The present invention relates to a method of increasing resistance against fungal pathogens of the order Pucciniales, preferably the family Phacopsoraceae,in plants and/or plant cells. This is achieved by increasing the expression of an RLK1protein or fragment thereof in a plant, plant part and/or plant cell in comparison to wild type plants, wild type plant parts and/or wild type plant cells. Furthermore, the invention relates to transgenic plants, plant parts, and/or plant cells having an increased resistance against fungal pathogens, in particular, pathogens of the order Pucciniales, preferably the family Phacopsoraceae, and to recombinant expression vectors comprising a sequence that is identical or homologous to a sequence encoding an RLK1protein.

The disclosure provides a novel method for treating genetic disorders where a peptide sequence targets proteins produced via gene therapy into exosomes. These protein-loaded exosomes can enter into non-transduced cells and correct pathology. Also, gene therapy compositions, protein replacement therapy composition, pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and the recombinant proteins are also disclosed. The method can also be used to improve in vitro recombinant protein yield.

Described herein is a previously unknown function of XBP1 in controlling anti-tumor immunity. It is shown that inhibiting XBP1 in tumor-associated dendritic cells inhibits tumor growth and induces protective anti-tumor immune responses.

Described herein is a previously unknown function of XBP1 in controlling anti-tumor immunity. It is shown that inhibiting XBP1 in tumor-associated dendritic cells inhibits tumor growth and induces protective anti-tumor immune responses.

Kinases can be engineered to utilize an ATP analog that is not readily utilized by wild-type kinases by introducing a mutation in the ATP-binding pocket. However, application of this method has been limited by the membrane impermeability of the ATP analog. Provided herein are methods for in situ visualization of substrates of an analog-sensitive kinase, the method comprising a mild fixation step. Also provided herein are kits comprising a fixative, an ATP analog, and an agent for detecting the substrates modified by the ATP analog.

The present invention relates to a modified microorganism having, compared to its wildtype, a reduced activity of an enzyme encoded by the ptsA-gene, a reduced activity of an enzyme encoded by the ptsH-gene or a reduced activity of an enzyme encoded by the ptsA-gene and a reduced activity of an enzyme encoded by the ptsH-gene, wherein the wildtype from which the modified microorganism has been derived belongs to the family of Pasteurellaceae. The present invention also relates to a method for producing succinic acid and to the use of modified microorganisms.

The invention provides compositions (e.g., pharmaceutical compositions) comprising nucleic acids encoding the serine/threonine kinase PIM-1, and methods for making and using them; including methods for inducing cellular proliferation, and protecting cardiac cells from hypoxia and cellular apoptosis. The invention provides compositions (e.g., pharmaceutical compositions) comprising nucleic acids encoding PIM-1, and methods for enhancing the regenerative potential of stem cells in the heart.

Disclosed in the present application is a compound of formula (I) as defined herein as well as a pharmaceutical composition comprising said compound. Further disclosed in the present application is the use of such pharmaceutical compositions for treating diseases, namely inter alia for use in the treatment of cancer, metabolic, inflammatory, autoimmune and viral diseases. The compounds disclosed herein are inhibitors of MNK1 and/or MNK2 kinases.

##STR00001##